Abstract The primary objective of the Physiology Core is to provide DRC members with access to centralized facilities, services and technical expertise to address complex metabolic questions related to diabetes using normal, diabetic or genetically modified rodent models. The core is structured into two Sub-cores, the Animal Surgery and Experimental Procedure Sub-core and the Analytical Sub-core, each of which contains specialized equipment and key personnel to help DRC investigators and/or their trainees achieve their tasks in the most efficient and cost-effective manner. It also serves as a forum for collaboration between members with different research backgrounds, but a common interest in studying diabetes. Through the Animal Surgery and Experimental Procedure Sub-core, DRC investigators gain access to training, equipment, laboratory facilities and technical expertise to perform complex rodent surgeries, including the placement of vascular catheters and other implantables, such as brain micro-injection and micro-dialysis probes. Core staff help carry out complex metabolic studies using specialized experimental methodologies (e.g. glucose clamps, tracers, microdialysis and amperometric studies) in conscious mice and rats ? skills that are not easily accessible to investigators without previous training or experience, particularly young investigators, fellows, and pilot award recipients. The Analytical Sub-core provides DRC members with a central facility for the measurement of glucoregulatory hormones, cytokines and neurotransmitters specifically derived from rodent studies. This component of the Physiology Core benefits from the expertise and equipment of an on-going and prolific radioimmunoassay and HPLC facility. Expansion of the repertoire of mass spectrometry-based assays and establishment of a DRC - Mass Spectrometry Shared Resource to measure cytokines and neurotransmitters and to offer state-of-the-art proteomic methods of protein detection and post-translational modification quantification will serve to greatly enhance the value of this core to the DRC investigator community. Together, these two sub-cores provide DRC members with the unique opportunity to systematically address pertinent mechanistic questions in vivo and to assess metabolic changes in both the central nervous system and peripheral tissues in the most efficient and economical manner.